Nucleic Acid Inhibitors Flashcards by Aisha Farah

Which are the Fuoroquinolones

Ciprofloxacin
Levofloxacin
Gemifloxacin
Monifloxacin

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Fluoroquinolones are derived from

Nalidixic Acid which is the Quinolone Mother Substance

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Spectrum/Uses of Ciprofloxacin

Narrow spectrum
Potent activity against Gram-negative aerobic organisms
Enterococci
Pseudomonas Aeruginosa
Haemophilus
Neisseria
Legionelle

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Ciprofloxacin is used for

DOC for Typhoid fever
Cystitis
Meningococcal Prophylaxis
LRT Infections

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What is Ciprofloxacin not used for

Gram +ive bacteria (Streptococci and Pnemococci)
Anaerobic bacteria
Gonorrhoea

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Spectrum/Uses of Moxifloxacin, Gemifloxacin and Levofloxacin

Active against Gram +ive
LRTis
Acute sinusitis
Skin infections

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Levofloxacin is used to treat

UTI
Soft tissue infections
M.Tuberculosis

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Moxifloxacin is used to treat

M.Tuberculosis

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When are Moxifloxacin, Gemifloxacin and Levofloxacin used to treat Respiratory infections

In cases of B-Lactam allergy

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Spectrum/uses of Norfloxacin

Only used in UTIs
Wider spectrum
Structurally similar to Nalidixic acid

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Spectrum/Uses of Nalidixic acid

Very narrow spectrum of activity
Gram -ive bacteria: acute and chronic LUTIs

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What can the use of Nalidixic Acid result in

Quinolone resistance

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Why is Nalidixic acid only indicated for LUTIs

Because it doesn’t achieve sustemic antibacterial levels

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MOA of Fluoroquinolones

Inhibit Topoisomerase II (DNA Gyrase)
Inhibit Topoisomerase IV
Bactericidal

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Inhibition of Topoisomerase II causes

-It prevents the relaxation of +ively supercoiled DNA required for normal transcription and replication
-it also inhibits the cutting and joining action of the enzyme on DNA double helix

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Inhibition of Topoisomerase IV causes

-It prevents the removal of supercoils by the enzyme
-it interferes with separation of replicated chromosomal DNA into respective daughter cells during cell division

Resistance Mechanism against Fluoroquinolones

One or more point mutation in Quinolone binding region of target enzyme
Change in permeability

How are Fluoroquinolones administered

Orally or IV
Best taken on empty stomach: 1-2hrs before or 2-3hrs after
Adequate fluid must be taken

Absorption of Fluoroquinolones are impaired by what?

by divalent cations (antacids, milk, yogurt)
Causes formation of a chelate

Why is adequate fluid intake needed for Fluoroquinolones?

it will prevent their crystallisation in urine

What should be avoided when taking Quinolones

excessive urine alkalinity becos the drugs would then precipitate in the urine and form crystal urea.

PK of Fluoroquinolones

Metabolized by CYP450 enzyme and some of them actually do inhibit this enzyme (Ciprofloxacin and Levofloxacin to a lower extent)

SEs of Fluroquinolones

GIT disturbances and skin rashes
Seizure risk (exp. Ciprofloxacin)
Hallucinations (rare but in elderly)
Hyperglycaemia in diabteics
Hypoglycameia Type 2 diabetics who are receiving oral hypoglycemic agents
Damage to Growing cartilage and cause arthropathy+arthralgia
Incr. risk of Tendonitis and tendon rupture
Peripheral Neuropathy with incr. time of exposure
Photosensitivity
Rarely aortic aneurysm

SEs of Nalidixic acid

Neurotoxic
Cause Photosensitivity
Could cause seizures

Caution for Nalidixic acid

Elderly as it causes Neurotoxicity

DIS of Fluoroquinolones

Ciprofloxacin+ theophylline Warfarin+ Ciprofloxacin NSAIDs: lower seizure threshold= increase. risk of seizures Oral hypoglycemic agents: gibenclamide Cipro+Levo may interfere with agents that prolong QT interval Antacids/minerals Probencid

Cautions/CIs of Fluroqionolones

Epilepsy (Nalidixic acid CI) Hepatic failure Pregnancy/lactation Babies/children <18yrs Renal Failure (Nalidixic acid) Porphyria (Nalidixic acid) Elderly patients allergy G6PD deficiency

Spectrum of Metronidazole

powerful antibacterial action against Anaerobic Organisms Bactericidal Antiprotozoal action on trophozoites

Uses of Metronidazole

H.Pylori (PPI+amoxicillin+metronidazole) Giardiasis: parasitic infection Acute necrotizing Ulcerative gingivitis Pseudomembranous colitis Topical for Rosacea and bacterial vaginosis

MOA of Metronidazole

Undergoes reduction steps to form reactive intermediates These intermediates then react with DNA like macromolecules and cause: -Alterations in DNA Helix -Breaking of DNA chain

Resistance mechanisms against Metronidazole

Decreased uptake increased removal decreased activation in bacteria Altered enzymes that convert active metronidazole to non-toxic derivatives

Admin of Metronidazole

Orally with water=near total ansorp. Rectal, IV and Topically

PK of Metronidazole

metabolised in liver 10-20 excreted unchanged in urine

SEs of Metronidazole

Nausea, headache, dry mouth Metallic taste Mild GIT discomfort Inhibits alcohol metabolism--> acetaldehyde dehydrogenase inhibited=acetaldehyde accumulates= Disulfiram-like effect CNS effects Possible dark colored urine

Additional SEs of Metronidazole in Older patients

Blood counts when used long-term History of Blood Dyscrasias

DIs of Metronidazole

Cimetidine: M. metabolism decr. Phenobarbitone: M. metabolism incr. Phenytoin: M. metabolism decr. Warfarin: anticoagulant effect incr= incr. risk of bleeding Alcohol: decreased metabolism Lithium: plasma levels incr.=toxicity Disulfiram

CI of Metronidazole

Alcohol use

Caution with Metronidazole

Epilepsy Porphyria CNS disease Impaired hepatic function 1st Trimester of pregnancy (can be used in other trimesters) Lactation